Until the early 1990s, it remained largely unclear how the immune system could recognize antigens on autologous cells and specific tumor cell recognition by T cells was doubted by many researchers. In 1991, the first description of antigens specifically expressed on melanoma cells formed the basis for a new era of molecularly defined tumor immunology . In the following years, numerous antigens, either overexpressed or specifically expressed on tumor cells, have been characterized and respective HLA-restricted epitopes that are capable of triggering CD8 and CD4 T cell responses have been identified . With the introduction of dendritic cell culture and demonstration of their T cell stimulatory capacity by Steinmann et al., therapeutic approaches have been developed during the last years that aim at inducing tumor-antigen (TAA) specific T cell responses for the treatment of tumor patients . These approaches are based on the assumption that the immune system of tumor patients is mainly unresponsive for antigens on autologous tumors.
Division of Cellular Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany
E. Yefenof (ed.), Innate and Adaptive Immunity in the Tumor Microenvironment. © Springer 2008
The induction of protective T cell responses depends on fully activated antigen presenting cells, e.g. dendritic cells (DCs). During infectious diseases DCs are activated in inflamed tissues by so called "danger signals". Danger signals are provided by conserved molecular signatures of pathogens such as double stranded RNA molecules or hypomethylated DNA motifs and recognized by respective toll like receptors on cells of the innate immune system, including DCs, which enables them to recognize the presence and general class of the infectious pathogen .
Tumor tissue, as autologous "self' is widely assumed to lack danger signals. This assumption was substantiated by findings that significant proportions of natural TAA-specific CD8 T cells as isolated by the HLA-tetramer technology from the peripheral blood of the patients were non-functional .
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